The major effort during the next year will be devoted towards the study of the quaternary antifibrillatory drugs in the recently developed animal model in which coronary thrombosis develops in the awake, ambulatory dog. We believe this approach will help to identify those agents that have the greatest potential to be of value in a clinical therapeutic situation. Since many of the animals develop "primary ventricular fibrillation" or sudden cardiac death, the model should provide important information on the antifibrillatory potential of the drugs under study. We plan to examine bretylium and UM-360, an analog of bretylium, which lacks adrenergic neuronal blocking actions. UM-424 as well as related derivatives will be studied using the conscious animal model prone to sudden cardiac death. A new quaternary drug, clofilium will be subjected to critical analysis because of promising preliminary data. Recently, we have developed methods in which animals can be studied in the unanesthetized state several days after the experimental induction of acute myocardial infarction. Programmed electrical pacing of the heart is able to induce runs of ventricular tachycardia and/or ventricular fibrillation. The technique is similar to the methods used clinically in which programmed stimulation of the heart for the purpose of determining the susceptibility of developed disturbances of ventricular rhythm. We would hope to compare new antiarrhythmic agents (flecainide, N-acetylprocainamide, RMI-81968A, amiodarone, encainide, etc.) to quaternary drugs to see if the latter agents possess any distinct advantage in the ischemic heart.